CA1328105C - Derives d'alcanolamines utilises comme agents cardiovasculaires - Google Patents

Derives d'alcanolamines utilises comme agents cardiovasculaires

Info

Publication number: CA1328105C
Authority: CA; Canada
Prior art keywords: compound; hydroxy; amino; phenoxy; phenyl
Prior art date: 1988-07-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000605462A

Other languages

English (en)

Inventor

Randall Edward Lis

William Carl Lumma, Jr.

Thomas Kenneth Morgan, Jr.

Klaus Nickisch

Ronald Andre Wohl

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Pharma AG

Original Assignee

Schering AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1988-07-13

Filing date

1989-07-12

Publication date

1994-03-29

1989-07-12 Application filed by Schering AG filed Critical Schering AG

1994-03-29 Application granted granted Critical

1994-03-29 Publication of CA1328105C publication Critical patent/CA1328105C/fr

2011-03-29 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000002327 cardiovascular agent Substances 0.000 title abstract description 4
229940125692 cardiovascular agent Drugs 0.000 title abstract description 4
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 125
239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 46
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 9
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
125000001841 imino group Chemical group [H]N=* 0.000 claims description 5
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
150000002923 oximes Chemical class 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims 3
230000003000 nontoxic effect Effects 0.000 claims 3
208000024172 Cardiovascular disease Diseases 0.000 claims 2
NZOGFGXEMJWMEH-UHFFFAOYSA-N 1-[(4-imidazol-1-ylphenyl)methylamino]-3-(2-methylphenoxy)propan-2-ol Chemical compound CC1=CC=CC=C1OCC(O)CNCC1=CC=C(N2C=NC=C2)C=C1 NZOGFGXEMJWMEH-UHFFFAOYSA-N 0.000 claims 1
YZUUILKYQVFYAE-UHFFFAOYSA-N 1-[2-(4-imidazol-1-ylphenoxy)ethylamino]-3-(3-methylphenoxy)propan-2-ol Chemical compound CC1=CC=CC(OCC(O)CNCCOC=2C=CC(=CC=2)N2C=NC=C2)=C1 YZUUILKYQVFYAE-UHFFFAOYSA-N 0.000 claims 1
LHDUUWAMFCDNEW-UHFFFAOYSA-N 1-[2-(4-imidazol-1-ylphenoxy)ethylamino]-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol Chemical compound C1=CC(CCOC)=CC=C1OCC(O)CNCCOC1=CC=C(N2C=NC=C2)C=C1 LHDUUWAMFCDNEW-UHFFFAOYSA-N 0.000 claims 1
XMLOXOFMPHIHFN-UHFFFAOYSA-N 1-[2-(4-imidazol-1-ylphenoxy)ethylamino]-3-phenoxypropan-2-ol Chemical compound C=1C=CC=CC=1OCC(O)CNCCOC(C=C1)=CC=C1N1C=CN=C1 XMLOXOFMPHIHFN-UHFFFAOYSA-N 0.000 claims 1
JOLIPDIUTBJMAD-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[[1-(4-imidazol-1-ylphenoxy)-2-methylpropan-2-yl]amino]propoxy]phenyl]acetamide Chemical compound C=1C=C(CC(N)=O)C=CC=1OCC(O)CNC(C)(C)COC(C=C1)=CC=C1N1C=CN=C1 JOLIPDIUTBJMAD-UHFFFAOYSA-N 0.000 claims 1
BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
QZWUQVSQIFFFKY-UHFFFAOYSA-N ersentilide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CNCCOC1=CC=C(N2C=NC=C2)C=C1 QZWUQVSQIFFFKY-UHFFFAOYSA-N 0.000 claims 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
GSYAWOHAESBPCD-UHFFFAOYSA-N n-[2-[[2-hydroxy-3-(4-methoxyphenoxy)propyl]amino]ethyl]-4-imidazol-1-ylbenzamide Chemical compound C1=CC(OC)=CC=C1OCC(O)CNCCNC(=O)C1=CC=C(N2C=NC=C2)C=C1 GSYAWOHAESBPCD-UHFFFAOYSA-N 0.000 claims 1
BQOIBCUHZLZXDB-UHFFFAOYSA-N n-[2-[[2-hydroxy-3-[4-(methanesulfonamido)phenoxy]propyl]amino]ethyl]-4-imidazol-1-ylbenzamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CNCCNC(=O)C1=CC=C(N2C=NC=C2)C=C1 BQOIBCUHZLZXDB-UHFFFAOYSA-N 0.000 claims 1
QZWUQVSQIFFFKY-IBGZPJMESA-N n-[4-[(2s)-2-hydroxy-3-[2-(4-imidazol-1-ylphenoxy)ethylamino]propoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OC[C@@H](O)CNCCOC1=CC=C(N2C=NC=C2)C=C1 QZWUQVSQIFFFKY-IBGZPJMESA-N 0.000 claims 1
DBTRNVNGJVUGQX-UHFFFAOYSA-N n-[4-[1-hydroxy-2-[2-(4-imidazol-1-ylphenoxy)ethylamino]ethyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C(O)CNCCOC1=CC=C(N2C=NC=C2)C=C1 DBTRNVNGJVUGQX-UHFFFAOYSA-N 0.000 claims 1
DFMWOTVQIINEOY-UHFFFAOYSA-N n-[4-[2-hydroxy-3-[[1-(4-imidazol-1-ylphenoxy)-2-methylpropan-2-yl]amino]propoxy]phenyl]methanesulfonamide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1OCC(O)CNC(C)(C)COC(C=C1)=CC=C1N1C=CN=C1 DFMWOTVQIINEOY-UHFFFAOYSA-N 0.000 claims 1
WXAGJQFTYBUBAZ-UHFFFAOYSA-N n-[4-[4-(2-hydroxy-3-phenoxypropyl)piperazin-1-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1N1CCN(CC(O)COC=2C=CC=CC=2)CC1 WXAGJQFTYBUBAZ-UHFFFAOYSA-N 0.000 claims 1
PPZQGVVFRVQCOU-UHFFFAOYSA-N n-[4-[4-(2-hydroxy-3-phenoxypropyl)piperazine-1-carbonyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C(=O)N1CCN(CC(O)COC=2C=CC=CC=2)CC1 PPZQGVVFRVQCOU-UHFFFAOYSA-N 0.000 claims 1
HHBPPZCDEAGVIX-FQEVSTJZSA-N n-[4-[4-[(2s)-2-hydroxy-3-(2-methylphenoxy)propyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound CC1=CC=CC=C1OC[C@@H](O)CN1CCN(C=2C=CC(NS(C)(=O)=O)=CC=2)CC1 HHBPPZCDEAGVIX-FQEVSTJZSA-N 0.000 claims 1
HHBPPZCDEAGVIX-UHFFFAOYSA-N n-[4-[4-[2-hydroxy-3-(2-methylphenoxy)propyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound CC1=CC=CC=C1OCC(O)CN1CCN(C=2C=CC(NS(C)(=O)=O)=CC=2)CC1 HHBPPZCDEAGVIX-UHFFFAOYSA-N 0.000 claims 1
QNDDXCZGZXSBCC-UHFFFAOYSA-N n-[4-[4-[2-hydroxy-3-(3-methylphenoxy)propyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound CC1=CC=CC(OCC(O)CN2CCN(CC2)C=2C=CC(NS(C)(=O)=O)=CC=2)=C1 QNDDXCZGZXSBCC-UHFFFAOYSA-N 0.000 claims 1
GGJBLPUTILVLNH-UHFFFAOYSA-N n-[4-[4-[2-hydroxy-3-[(5-oxo-7,8-dihydro-6h-naphthalen-1-yl)oxy]propyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1N1CCN(CC(O)COC=2C=3CCCC(=O)C=3C=CC=2)CC1 GGJBLPUTILVLNH-UHFFFAOYSA-N 0.000 claims 1
KGHMBTJPFPFRKU-UHFFFAOYSA-N n-[4-[4-[2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl]piperazine-1-carbonyl]phenyl]methanesulfonamide Chemical compound C1=CC(CCOC)=CC=C1OCC(O)CN1CCN(C(=O)C=2C=CC(NS(C)(=O)=O)=CC=2)CC1 KGHMBTJPFPFRKU-UHFFFAOYSA-N 0.000 claims 1
WFCXENJCPDJVBY-UHFFFAOYSA-N n-[4-[[(2-hydroxy-3-phenoxypropyl)amino]methyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CNCC(O)COC1=CC=CC=C1 WFCXENJCPDJVBY-UHFFFAOYSA-N 0.000 claims 1
PCRICIUMMKDSIF-UHFFFAOYSA-N n-[4-[[[2-hydroxy-3-(3-methylphenoxy)propyl]amino]methyl]phenyl]methanesulfonamide Chemical compound CC1=CC=CC(OCC(O)CNCC=2C=CC(NS(C)(=O)=O)=CC=2)=C1 PCRICIUMMKDSIF-UHFFFAOYSA-N 0.000 claims 1
JBIIIJUBMKGJTB-UHFFFAOYSA-N n-[4-[[[2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl]amino]methyl]phenyl]methanesulfonamide Chemical compound C1=CC(CCOC)=CC=C1OCC(O)CNCC1=CC=C(NS(C)(=O)=O)C=C1 JBIIIJUBMKGJTB-UHFFFAOYSA-N 0.000 claims 1
230000003288 anthiarrhythmic effect Effects 0.000 abstract description 3
230000001747 exhibiting effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 267
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
239000002904 solvent Substances 0.000 description 76
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
229910001868 water Inorganic materials 0.000 description 63
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 55
239000000243 solution Substances 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
239000000203 mixture Substances 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
238000002360 preparation method Methods 0.000 description 23
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
229910000041 hydrogen chloride Inorganic materials 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 16
HNQIVZYLYMDVSB-NJFSPNSNSA-N methanesulfonamide Chemical compound [14CH3]S(N)(=O)=O HNQIVZYLYMDVSB-NJFSPNSNSA-N 0.000 description 15
238000010992 reflux Methods 0.000 description 15
239000007787 solid Substances 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 14
-1 imidazol-1-ylphenyl Chemical group 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
239000010410 layer Substances 0.000 description 13
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 12
239000000284 extract Substances 0.000 description 12
150000003839 salts Chemical class 0.000 description 12
238000003756 stirring Methods 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
238000000034 method Methods 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
206010003119 arrhythmia Diseases 0.000 description 10
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
230000006793 arrhythmia Effects 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
239000000499 gel Substances 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 8
239000012458 free base Substances 0.000 description 8
239000001294 propane Substances 0.000 description 8
150000001408 amides Chemical class 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
239000012141 concentrate Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 6
150000002118 epoxides Chemical class 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 6
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
FQYUMYWMJTYZTK-UHFFFAOYSA-N Phenyl glycidyl ether Chemical compound C1OC1COC1=CC=CC=C1 FQYUMYWMJTYZTK-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
239000007789 gas Substances 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
229960003712 propranolol Drugs 0.000 description 5
230000009467 reduction Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
206010049418 Sudden Cardiac Death Diseases 0.000 description 4
230000009471 action Effects 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000003814 drug Substances 0.000 description 4
230000002526 effect on cardiovascular system Effects 0.000 description 4
238000009472 formulation Methods 0.000 description 4
LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
238000007327 hydrogenolysis reaction Methods 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
239000000047 product Substances 0.000 description 4
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
239000000725 suspension Substances 0.000 description 4
229940086542 triethylamine Drugs 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
229910017974 NH40H Inorganic materials 0.000 description 3
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
238000013459 approach Methods 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000000969 carrier Substances 0.000 description 3
150000003943 catecholamines Chemical class 0.000 description 3
229940079593 drug Drugs 0.000 description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
238000001914 filtration Methods 0.000 description 3
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
150000002576 ketones Chemical group 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 3
230000008569 process Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000036279 refractory period Effects 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 3
ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 3
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238000005984 hydrogenation reaction Methods 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
229940039009 isoproterenol Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229960001861 melperone Drugs 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
KNLMNIUUGKBEDX-UHFFFAOYSA-N methyl 2-(1h-imidazol-2-yl)benzoate Chemical class COC(=O)C1=CC=CC=C1C1=NC=CN1 KNLMNIUUGKBEDX-UHFFFAOYSA-N 0.000 description 1
KUBBZTZQWIGHFH-UHFFFAOYSA-N methyl 4-imidazol-1-ylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C=NC=C1 KUBBZTZQWIGHFH-UHFFFAOYSA-N 0.000 description 1
229960002237 metoprolol Drugs 0.000 description 1
IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
DEFIRISSBZLCHM-UHFFFAOYSA-N n',n'-dibenzyl-n-propylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCNCCC)CC1=CC=CC=C1 DEFIRISSBZLCHM-UHFFFAOYSA-N 0.000 description 1
ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
GXELTROTKVKZBQ-UHFFFAOYSA-N n,n-dibenzylhydroxylamine Chemical class C=1C=CC=CC=1CN(O)CC1=CC=CC=C1 GXELTROTKVKZBQ-UHFFFAOYSA-N 0.000 description 1
RNUDNTDOHGXZOR-UHFFFAOYSA-N n,n-dibenzylnitramide Chemical class C=1C=CC=CC=1CN([N+](=O)[O-])CC1=CC=CC=C1 RNUDNTDOHGXZOR-UHFFFAOYSA-N 0.000 description 1
KVLWJWXPFLSTCH-UHFFFAOYSA-N n-(2-aminoethyl)-4-imidazol-1-ylbenzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCN)=CC=C1N1C=NC=C1 KVLWJWXPFLSTCH-UHFFFAOYSA-N 0.000 description 1
BRDHOCVMWSXEHI-UHFFFAOYSA-N n-(4-cyanophenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=C(C#N)C=C1 BRDHOCVMWSXEHI-UHFFFAOYSA-N 0.000 description 1
DMBDRKKEZLXIBV-UHFFFAOYSA-N n-[4-(oxiran-2-ylmethoxy)phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC1OC1 DMBDRKKEZLXIBV-UHFFFAOYSA-N 0.000 description 1
VLWJKVNMRMHPCC-UHFFFAOYSA-N n-benzyl-2-chloro-n-(2-chloroethyl)ethanamine Chemical compound ClCCN(CCCl)CC1=CC=CC=C1 VLWJKVNMRMHPCC-UHFFFAOYSA-N 0.000 description 1
RAJZCNAPSJZGBF-UHFFFAOYSA-N n-benzyl-2-chloroethanamine;hydrochloride Chemical compound [Cl-].ClCC[NH2+]CC1=CC=CC=C1 RAJZCNAPSJZGBF-UHFFFAOYSA-N 0.000 description 1
FVLVBVSILSHUAF-UHFFFAOYSA-N n-benzyl-3,5-dimethyl-n-propan-2-ylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(C(C)C)CC1=CC=CC=C1 FVLVBVSILSHUAF-UHFFFAOYSA-N 0.000 description 1
VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
229960004255 nadolol Drugs 0.000 description 1
229950000754 nipradilol Drugs 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000003540 papillary muscle Anatomy 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
230000037361 pathway Effects 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002028 premature Effects 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
210000003742 purkinje fiber Anatomy 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000033764 rhythmic process Effects 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical class N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
230000007017 scission Effects 0.000 description 1
KHYPYQZQJSBPIX-UHFFFAOYSA-N sematilide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(NS(C)(=O)=O)C=C1 KHYPYQZQJSBPIX-UHFFFAOYSA-N 0.000 description 1
229950008118 sematilide Drugs 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BPSUJSDZHLTNJR-UHFFFAOYSA-N sulfamide;hydrochloride Chemical compound Cl.NS(N)(=O)=O BPSUJSDZHLTNJR-UHFFFAOYSA-N 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
UMFCIIBZHQXRCJ-NSCUHMNNSA-N trans-anol Chemical compound C\C=C\C1=CC=C(O)C=C1 UMFCIIBZHQXRCJ-NSCUHMNNSA-N 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA000605462A 1988-07-13 1989-07-12 Derives d'alcanolamines utilises comme agents cardiovasculaires Expired - Fee Related CA1328105C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US218,195		1988-07-13
US07/218,195 US5051423A (en)	1988-07-13	1988-07-13	Derivatized alkanolamines as cardiovascular agents

Publications (1)

Publication Number	Publication Date
CA1328105C true CA1328105C (fr)	1994-03-29

Family

ID=22814120

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000605462A Expired - Fee Related CA1328105C (fr)	1988-07-13	1989-07-12	Derives d'alcanolamines utilises comme agents cardiovasculaires

Country Status (9)

Country	Link
US (1)	US5051423A (fr)
EP (1)	EP0358284B1 (fr)
JP (1)	JPH07119193B2 (fr)
AT (1)	ATE157089T1 (fr)
CA (1)	CA1328105C (fr)
DE (1)	DE68928262T2 (fr)
ES (1)	ES2107998T3 (fr)
GR (1)	GR3025151T3 (fr)
WO (1)	WO1990000548A2 (fr)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU7997091A (en) *	1990-05-30	1991-12-31	American Home Products Corporation	Substituted arylsulfonamides and benzamides
EP0524146A1 (fr) *	1991-07-19	1993-01-20	Ciba-Geigy Ag	Dérivés de pipérazine substitués par un groupe amino
US5202346A (en) *	1992-02-25	1993-04-13	American Home Products Corporation	Piperidinyl and piperazinyl derivatives
US5254689A (en) *	1992-02-25	1993-10-19	American Home Products Corporation	Piperdinyl and piperazinyl derivatives
US5384319A (en) *	1993-01-06	1995-01-24	Ciba-Geigy Corporation	Aminoalkylphenyl compounds
US5380726A (en) *	1993-01-15	1995-01-10	Ciba-Geigy Corporation	Substituted dialkylthio ethers
US5451677A (en) *	1993-02-09	1995-09-19	Merck & Co., Inc.	Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity
WO1999029672A1 (fr) *	1997-12-05	1999-06-17	Eli Lilly And Company	AGONISTES β3-ADRENERGIQUES SPECIFIQUES
US6537994B2 (en) *	2000-07-17	2003-03-25	Wyeth	Heterocyclic β3 adrenergic receptor agonists
CN1469876A (zh) *	2000-10-20	2004-01-21	�Ʒ�	α-芳基乙醇胺及其用作β-3肾上腺素能受体激动剂的用途
AU2002322720B2 (en)	2001-07-25	2008-11-13	Raptor Pharmaceutical Inc.	Compositions and methods for modulating blood-brain barrier transport
EP1453804B1 (fr)	2001-11-30	2007-08-22	F. Hoffmann-La Roche AG	Antagonistes vii du recepteur ccr3
WO2003072547A1 (fr)	2002-02-27	2003-09-04	Pfizer Products Inc.	Procedes et intermediaires utiles dans la preparation d'agonistes du recepteur $g(b)3 adrenergique
US6864268B2 (en)	2002-02-27	2005-03-08	Pfizer Inc.	β3 adrenergic receptor agonists
WO2003072573A1 (fr) *	2002-02-27	2003-09-04	Pfizer Products Inc.	Formes cristallines de (r)-2-(2-(4-oxazol-4-yl-phenoxy)-ethylamino)-1-pyridin-3-yl-ethanol
US6982259B2 (en) *	2002-04-30	2006-01-03	Schering Aktiengesellschaft	N-heterocyclic derivatives as NOS inhibitors
US20050075323A1 (en) *	2003-03-05	2005-04-07	Pfizer Inc	Beta3 adrenergic receptor agonists and uses thereof
CA2789262C (fr)	2005-04-28	2016-10-04	Proteus Digital Health, Inc.	Systeme pharma-informatique
EP2063905B1 (fr)	2006-09-18	2014-07-30	Raptor Pharmaceutical Inc	Traitement des troubles hépatiques par l'administration de conjugués de protéine associée au récepteur (rap)
TR201908314T4 (tr)	2009-02-20	2019-06-21	2 Bbb Medicines B V	Glutatyon bazlı ilaç dağıtım sistemi.
KR101909711B1 (ko)	2009-05-06	2018-12-19	라보라토리 스킨 케어, 인크.	활성제-칼슘 포스페이트 입자 복합체를 포함하는 피부 전달 조성물 및 이들을 이용하는 방법
US20120077778A1 (en)	2010-09-29	2012-03-29	Andrea Bourdelais	Ladder-Frame Polyether Conjugates

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Publication number	Priority date	Publication date	Assignee	Title
CA967965A (en) *	1968-12-24	1975-05-20	Hoffmann-La Roche Limited	Aromatic ethers and process for the manufacture thereof
GB1301134A (en) *	1970-07-18	1972-12-29	Pfizer Ltd	SUBSTITUTED 1-PHENYL-2-ALLYLAMINO-ALKANOLS, 1-PHENYL-2-ALLYLAMINO-ALKANES AND alpha-AMINOALKYLPHENYL KETONES
GB1509527A (en) *	1974-06-05	1978-05-04	Ici Ltd	1-(aryl-or heteroaryl)oxy-3-(substituted-amino)propan-2-ol derivatives processes for their manufacture and pharmaceutical compositions containing them
CA1120058A (fr) *	1978-07-03	1982-03-16	Jack Mills	Phenetolamines, compositions et potentialisation des medicaments oncolytiques
DE3023369A1 (de) *	1980-06-23	1982-01-14	Boehringer Mannheim Gmbh, 6800 Mannheim	Aryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE3101456A1 (de) *	1981-01-19	1982-09-02	Basf Ag, 6700 Ludwigshafen	Phenylpiperazinyl-propanole von hetarylphenolen, ihre herstellung und diese enthaltende therapeutische mittel
EP0068669A1 (fr) *	1981-06-20	1983-01-05	Beecham Group Plc	Phényléthanolamines secondaires, procédés de leur préparation et leur application pharmaceutique
GB8619472D0 (en) *	1986-08-09	1986-09-17	Pfizer Ltd	Anti-arrhythmia agents
US4804662A (en) *	1987-05-05	1989-02-14	Schering A.G.	Substituted 4-(1H-imidazol-1-yl)benzamides as antiarrhythmic agents
US4851526A (en) *	1987-09-04	1989-07-25	Schering A.G.	1-(4-Substituted phenyl)-1H-imidazoles compounds

1988
- 1988-07-13 US US07/218,195 patent/US5051423A/en not_active Expired - Lifetime
1989
- 1989-07-12 CA CA000605462A patent/CA1328105C/fr not_active Expired - Fee Related
- 1989-07-13 JP JP1507740A patent/JPH07119193B2/ja not_active Expired - Lifetime
- 1989-07-13 ES ES89250001T patent/ES2107998T3/es not_active Expired - Lifetime
- 1989-07-13 AT AT89250001T patent/ATE157089T1/de not_active IP Right Cessation
- 1989-07-13 DE DE68928262T patent/DE68928262T2/de not_active Expired - Lifetime
- 1989-07-13 WO PCT/EP1989/000807 patent/WO1990000548A2/fr not_active Ceased
- 1989-07-13 EP EP89250001A patent/EP0358284B1/fr not_active Expired - Lifetime
1997
- 1997-10-22 GR GR970402784T patent/GR3025151T3/el unknown

Also Published As

Publication number	Publication date
DE68928262T2 (de)	1998-04-02
JPH07119193B2 (ja)	1995-12-20
WO1990000548A3 (fr)	1990-05-03
EP0358284A3 (fr)	1990-06-20
ES2107998T3 (es)	1997-12-16
US5051423A (en)	1991-09-24
GR3025151T3 (en)	1998-02-27
EP0358284A2 (fr)	1990-03-14
EP0358284B1 (fr)	1997-08-20
DE68928262D1 (de)	1997-09-25
JPH03501617A (ja)	1991-04-11
WO1990000548A2 (fr)	1990-01-25
ATE157089T1 (de)	1997-09-15

Legal Events

Date	Code	Title	Description
2002-04-02	MKLA	Lapsed

Publication	Publication Date	Title
CA1328105C (fr)	1994-03-29	Derives d'alcanolamines utilises comme agents cardiovasculaires
AU701420B2 (en)	1999-01-28	Novel piperazides derived from arylpiperazine, processes for their preparation, their use as medicaments and pharmaceutical compositions comprising them
AU758246B2 (en)	2003-03-20	N,N-substituted cyclic amine derivatives
FI66371B (fi)	1984-06-29	Foerfarande foer framstaellning av heterocykliska oxipropanolaminderivater
US5472961A (en)	1995-12-05	Acetamides
SK6252000A3 (en)	2001-11-06	Indazole bioisostere replacement of catechol in therapeutically active compounds
AU761422B2 (en)	2003-06-05	Compounds and methods for treatment of asthma, allergy and inflammatory disorders
EP0290377B1 (fr)	1994-03-02	[1H-Imidazolyl-1]-4 benzamides substitués en tant qu'agents antiarythmiques
US4851526A (en)	1989-07-25	1-(4-Substituted phenyl)-1H-imidazoles compounds
JPH0351708B2 (fr)	1991-08-07
US4906634A (en)	1990-03-06	Novel N-[4-(aminosubstituted)phenyl]methanesulfonamides and their use as cardiovascular agents
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